The use of membrane-permeable and intracellular reducible molecules for drug or gene delivery has gained increasing attention. In this work, chitosan (CS) was modified with extending arms consisting of disulfide spacers and arginine (Arg) residues (CS-SS-Arg) as a novel non-viral carrier for gene delivery. The chemical structure of synthesized CS-SS-Arg was characterized by proton nuclear magnetic resonance ( 1H-NMR) spectroscopy. Cleavage of disulfide spacers by glutathione (GSH) and dithiothreitol due to thiol-disulfide exchange reactions indicates that CS-SS-Arg is likely reducible in cytoplasm. The CS-SS-Arg was allowed to condense green fluorescent protein (GFP) DNA to form self-organized nanoparticles with a diameter of 130 nm and zeta potential of 35 mV. The DNA was released from CS-SS-Arg/DNA nanoparticles over time in the presence of GSH. Transfection studies by confocal laser scanning microscopy demonstrate that CS-SS-Arg/DNA nanoparticles had a 48-h delay of GFP expression in human embryonic kidney 293 (HEK 293) cells; however, the GFP expression level was higher and more sustainable than that of its unmodified CS counterpart. These analytical results suggest that the Arg-rich bioreducible CS-SS-Arg/DNA nanoparticles are promising as a carrier for gene delivery.
ASJC Scopus subject areas
- Materials Chemistry